The Nature of the Diabetic Glomerulus: Pressure-Induced and Metabolic Aberrations

Abstract

Early clinical and experimental studies on the pathogenesis of diabetic glomerulosclerosis identified specific mechanisms believed to be unique and crucial in the development and progression of the glomerular lesion. The relative importance of these mechanisms, broadly classified as hemodynamic or metabolic, has been long debated The hemodynamic factors included systemic arterial hypertension [1–3], glomerular hyperfunction and increased glomerular capillary hydrostatic pressure [4–6]. The metabolic factors related to changes associated with glomerular hypertrophy [7–9], hyperlipidemia [10, 11] and the effects of hyperglycemia exerted either directly [12–14] or through the formation of advanced glycosylation end products [15–17] and increased polyol pathway activity [18]. More recent studies have demonstrated that stimulated cytokine expression is also an important pathogenetic component [19–21]. These cytokines, specially transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) have been shown to induce extracellular matrix (ECM) deposition in glomeruli and to stimulate the mesangial cell synthesis of ECM components [22–25].